AB1488 GENOTYPE-PHENOTYPE CORRELATIONS OF FAMILIAL MEDITERRANEAN FEVER IN ARMENIAN POPULATION
Authors: M. Osipyan, M. Efraimidou, K. Ginosyan, A. Antikyan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an autoinflammatory disorder that mostly affects people of Middle Eastern and Mediterranean descent, and is characterized by recurrent and self-limiting episodes of fever, serositis, arthritis and etc. Although many studies in scope of the connection of the MEFV gene variants and clinical manifestation have been carried out since the discovery of the gene, there is not yet in detail data about Armenian population peculiarities and differences in the severity of the disease between the genotypes. <h3>Objectives</h3> The aim of this study is to compare the severity of the disease between different FMF genotypes and propose utilization of genotype assessment as a predictor for the disease progression. <h3>Methods</h3> 184 Armenian patients were included in the study. All patients fulfilled Tel-Hashomer classification criteria for FMF. Patients were studied following a standard protocol. 12 most frequent mutations of MEFV gene (E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S and R761H) were evaluated and according to the genotype patients were grouped in homozygotes, compound heterozygotes, heterozygotes and patients without mutations. Disease activity was measured by Tel-Hashomer severity score. <h3>Results</h3> 76,63% of examined patients were male and 23,4% -female. The mean age of the group was 41,53±18,73 years and the average duration of the disease- 11,42±8,5 years. Clinical manifestation of the patients included in the study were following: episodes of fever- 124 (67,39%), abdominal pain -120 (65,2%), pleuritis - 154 (83,696%), pericarditis -11 (0,0598%) arthritis -54 (29,348%), arthralgia -101 (54,89%), erysipelas-like erythema -22(11,9565%), splenomegaly -59(32,065%), amyloidosis-6(3,26%). 118 (64,13%)of patients carried any of the MEFV examined mutations and despite the presence of clinical manifestations 66 patients (35,87%) have no mutations detected. 21 (17,8%) of patients with mutation were homozygote, 65 (55,08%)compound heterozygote and 32 (27,11 %) heterozygote. The prevalence of MEFV mutations among examined patients was 61,3%, 28,4%, 21,65%, 5,04% accordingly for M694V, M680I, V726A, E148Q exons. Patients with M694V/M694V and M694V/M680I genotype had the highest Tel-Hashomer severity score (9,8±0,6 and 8,1±1,1 accordingly). Patients with homozygote genotype have earlier onset of the disease (p=0,02), more frequent attacks (p&lt;0,05), higher levels of ESR during the flare (P=0,009) compared with patient with other genotypes. No significant difference for the duration of the attack between different genotypes was found. Patients without any revealed mutations had the mildest disease presentations (Tel-Hashomer severity score – 3,2±1,6). <h3>Conclusion</h3> According to the data, age of the onset of FMF strongly correlates with the inherited genotype. Carriers of the MEFV gene mutations without any manifestations at early age should be expected to have onset years later and should be strongly monitored by clinicians. Despite the fact, that genotype is not included in Tel-Hashomer classification criteria, our study once more indicates, that not only phenotype but also genotype is very important for FMF. Further evaluation of bigger sample is required to describe the influence of the specific exons on the clinical manifestations. <h3>References</h3> [1]Ben-Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Rheum. 2009;61:1447–53. [PubMed] [2]Gershoni-Baruch R, Brik R, Shinawi M, Livneh A. The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever. Eur J Hum Genet. 2002;10:145–9. [PubMed] [3]Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum. 2003;48:1149–55. [PubMed] <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.